(A) Body weight index. The diabetic ZDF rats were significantly larger than the nondiabetic ZL rats. Canagliflozin administration in the ZL led to a significant reduction in body mass index that was absent in the ZDF diabetic rats. n = 8 to 10 per group. (B) Random glucose concentration on day of experiment. As expected, ZDF diabetic rats had significantly higher blood glucose concentrations compared to the nondiabetic ZL controls (p < 0.0001; n = 6 to 9 per group). Canagliflozin had no impact upon blood glucose in the ZL group (p = NS; n = 9 to 10 per group), but significantly reduced glucose in the diabetic ZDF rats (p < 0.0001; n = 6 to 9 per group). (C to E) Renal manifestations of diabetes in the ZDF rats. (C) Urine glucose, measured by urinalysis strip test. No glucosuria was detectable in the control ZL rats, but there was significant glucosuria in ZL rats on canagliflozin. As expected, significant glucosuria was found in both ZDF control and canagliflozin-treated groups. (D) Blood urea nitrogen was significantly higher in the ZDF rats compared with the nondiabetic ZL: 11 ± 2 mg/dl versus 19 ± 2 mg/dl (p = 0.006, n = 6 per group). (E) A similar pattern was observed in the urine albumin/creatinine ratio—the diabetic ZDF rats demonstrating a significantly higher albumin excretion compared with the nondiabetic ZL rat: 160 ± 39 mg/g versus 3,319 ± 577 mg/g (p = 0.0004; n = 4 to 5 per group). ZDF = Zucker Diabetic Fatty; ZL = Zucker Lean.